Poly (ADP ribose) (PAR) is a biopolymer of adenosine diphosphate ribose (ADPR) involved in diverse cellular processes, especially regulation of telomere length, DNA-damage response, stress granule formation and the regulation of biomolecular condensates. PAR serves as a protein post-translational modification altering a protein's interactions and activity. PAR is polymerized from NAD⁺ by poly (ADP-ribose) polymerase (PARP).

Synthesis

PAR is polymerized from oxidized nicotinamide adenine dinucleotide (NAD⁺) monomers by PARPs. NAD⁺ is added to protein substrates as a form of post-translational modification, referred to as PARylation or poly ADP-ribosylation. As subsequent NAD⁺ monomers are added, nicotinamide is lost and the free 1' position of the ADP ribose is bound to the 2' position of the previous ribose in the polymer chain. Polymerization can be reversed by poly (ADP-ribose) glycohydrolase (PARG).

Branching

Because monomers may be added to the 2' sites on both ribose sugars, PAR polymer branching occurs when ADP ribose is added to both ribose sugars of the previous single monomer in a chain. This branching is thought to increase the valency of PAR's interactions.

Function

Biomolecular condensates

Because biomolecular condensate formation often relies on highly-valent low-specificity interactions, PAR is thought to modulate a protein's ability to interact with these condensates. PARylation has been shown to be essential to the formation of stress granules, a form of biomolecular condensate and is suspected to be involved in others, especially in the nucleus, such as Cajal bodies.

DNA repair

PARP1 and 2 help perform DNA base excision repair through their catalytic activity.

Chromatin remodeling

PARPs can serve as epigenetic regulators through the PARylation of histones, causing local relaxation of chromatin and increased accessibility.

Telomere extension

PARP-5a and PARP-5b, also known as Tankyrase 1 and Tankyrase 2, serve to remove the telomerase inhibiting complex from telomeres through substrate PARylation.

Protein degradation

PARPs can serve to tag proteins for degradation by PARylation. Some ubiquitin ligases, such as RNF146 contain a PAR binding site to permit targeting to PARylated substrates for degradation in the wnt signaling pathway.